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A Structure‐Activity Investigation on Modified Analogues of an Argininocalixarene Based Non‐viral Gene Vector
Author(s) -
Lomazzi Michela,
Franceschi Valentina,
Bagnacani Valentina,
Vezzoni Carlo Alberto,
Donofrio Gaetano,
Casnati Alessandro,
Sansone Francesco
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100338
Subject(s) - linker , chemistry , cationic polymerization , calixarene , transfection , stereochemistry , alkyl , dna , gene delivery , viral vector , combinatorial chemistry , vector (molecular biology) , gene , genetic enhancement , recombinant dna , biochemistry , molecule , polymer chemistry , organic chemistry , computer science , operating system
The tetra‐L‐arginino‐tetrahexyloxycalix[4]arene 1 has shown extraordinary abilities to compact and internalize different types of Nucleid Acid cargos (DNA, microRNA, PNA) into cells even known to be transfected with great difficulties by commercial non‐viral gene delivery systems. This activity, accompanied by negligible toxicity, makes this calixarene a rather promising prototype of vector for Gene Therapy. In this study we report how small structural changes like i) the lower rim alkyl substituents, ii) the type of the terminal cationic headgroups (guanidinium or primary ammonium), iii) the length of the linker between the macrocycle and the terminal cationic headgroup, iv) the presence/absence of the basic α‐amino group of Arg, and v) the stereochemistry (L or D) of Arg, might affect the ability of the novel calixarene vectors to compact DNA and to deliver its cargo into the cells.